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Abstract
MicroRNAs (miRNAs) are regulatory molecules known to be aberrantly expressed in cancer and contribute to numerous aspects of tumor biology including the initiation, growth and spread of the tumor. With such diverse roles, it is becoming apparent that some may also provide valuable information which may be of use in a clinical setting, demonstrating the potential to act as both screening tools for the stratification of high-risk patients, while informing the treatment decision-making process. There is mounting evidence to suggest that some miRNAs may even provide assistance in the diagnosis of patients with breast cancer. In addition, miRNAs may themselves be considered therapeutic targets, with inhibition or reintroduction of a particular miRNA capable of inducing a response in vivo. This review focuses on miRNAs that have prognostic, diagnostic or predictive potential in breast cancer as well as the possible challenges in the translation of such observations to the clinic.
Acknowledgements
The authors would like to thank A Was for his kind assistance in the production of figures for this review. Funding is acknowledged from the Irish Research Council for Science, Engineering and Technology (IRCSET), Science Foundation Ireland through the Molecular Therapeutics for Cancer, Ireland Strategic Research Cluster (award 08/SRC/B1410; http://www.mtci.ie ) and the Irish Cancer Society Collaborative Cancer Research Centre BREAST-PREDICT grant, CCRC13GAL ( http://www.breastpredict.com ).
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
Key issues
In the last few years, miRNAs have demonstrated prognostic, predictive and diagnostic value in breast cancer and other diseases.
Particularly interesting is the ability to easily detect circulating miRNAs which could have diagnostic potential or assist in patient monitoring in a non-invasive fashion.
However, there are some technical challenges to be overcome in the translation of these results to a clinical setting.
Reliable quantitative real time-PCR methods of quantifying miRNAs in tissue and serum samples exist.
However, the use of quantitative real time-PCR precludes the evaluation of miRNAs in specific subsets of cells without the use of laser capture microdissection. As such, many profiling studies include miRNA expression from tumor, stromal, blood and immune cell sources.
In situ hybridization is a technically challenging alternative to visualize the specific pattern of expression of miRNAs in tissue sections.
Standardization of collection, storage and processing of miRNA samples must be made a priority if large-scale validation of diagnostic biomarkers is to be carried out.
miRNAs are relatively stable in formalin-fixed paraffin-embedded material opening up a vast quantity of archival material for use.
The use of miRNA signatures is promising. These can also be integrated with gene signatures.
Few miRNA biomarkers have been validated in multiple cohorts as the majority have been reported to be prognostic/diagnostic in standalone studies. Larger cohorts are needed to confirm these results.